Transcriptomic responses to acute or chronic ethanol exposure observed across five brain regions in male mice

Alcohol use disorder (AUD) has been consistently linked to transcriptomic dysregulation in the brain. Alcohol itself produces transcriptomic changes in the brain, and resulting molecular changes may contribute to the progression or maintenance of AUD. However, little is known about how ethanol-induced transcriptomic outcomes differ between acute and chronic exposure. Here, we systematically investigated the transcriptomic effects of ethanol exposure across key brain regions relevant to AUD and how these outcomes differ between acute and chronic exposure. To this end, RNA sequencing was done for the cortex, dorsal hippocampus, ventral hippocampus, dorsal striatum, and ventral striatum of adult male mice that were given a daily i.p. dose of ethanol or saline for 1 day (acute) or 10 days (chronic). Both ethanol exposure paradigms resulted in dysregulated expression (gene and transcript) and splicing in the investigated brain regions. Transcriptomic dysregulation varied across regions and was more robust following acute than chronic ethanol exposure. Paradigm-dependent transcriptional effects of ethanol were limited in most regions but were striking in the ventral hippocampus, suggesting alcohol's transcriptomic effects in this region might play a relevant role in the transition from limited to chronic alcohol consumption. Overall, this systematic study illuminates alcohol's effects on transcriptional regulation in the brain and how these effects differ across brain regions and by extent of exposure, ultimately providing valuable insight for developing novel therapeutics for AUD.